BACKGROUND: Brain volume loss (BVL) is accelerated in patients with multiple sclerosis (MS), occurring early in the disease course, and is associated with long-term disability worsening. To our knowledge, no prior network meta-analyses (NMAs) have been published assessing the relative efficacy of all treatments for relapsing MS (RMS) regarding BVL.
OBJECTIVES: To estimate the relative efficacy of teriflunomide versus other approved disease-modifying therapies (DMTs) in terms of BVL percentage change from baseline (CFB) at 12 and 24 months in patients with RMS using an NMA.
METHODS: MEDLINE, Embase, and CENTRAL were systematically searched up to August 2020 using a predefined search strategy and Population, Intervention, Comparators, Outcomes, and Study Type (PICOS) selection criteria for randomized controlled trials of DMTs in patients with RMS. Two reviewers independently reviewed the abstracts and publications; data on study design, patient characteristics, and outcomes were extracted in a predefined extraction file. Eighteen trials were assessed during the feasibility assessment and retained for the NMA. Bayesian NMAs using random-effects models were conducted using R and JAGS software. Sensitivity analyses, including pooled data for the OPERA I and II studies of ocrelizumab (where published data for the individual trials are not available), were also performed.
RESULTS: The primary NMAs of BVL percentage CFB to 12 and 24 months included 14 and 12 trials, respectively. Data were available for placebo and 11 DMTs: dimethyl fumarate, fingolimod, glatiramer acetate, intramuscular interferon β 1a, natalizumab, ocrelizumab (sensitivity analysis only), ofatumumab, ozanimod, ponesimod (24 months only), subcutaneous interferon β 1a, and teriflunomide. Primary results suggested numerical differences in favor of teriflunomide 14 mg versus most other treatments at each timepoint. At 12 months, there was statistically significant evidence in favor of teriflunomide 14 mg vs. natalizumab (mean difference in BVL percentage CFB [95% credible interval]: 0.47 [0.09-0.85]), ofatumumab (0.19 [0.02-0.36]), and placebo (0.31 [0.02-0.60]). Teriflunomide 14 mg has the highest probability of ranking best (0.598). At 24 months, there was statistically significant evidence in favor of teriflunomide 14 mg versus placebo (0.46 [0.04-0.88]). Estimates and conclusions from sensitivity analyses were consistent with those from the primary NMA. Further, results were in favor of teriflunomide 14 mg versus ocrelizumab at both 12 and 24 months (not statistically significant).
CONCLUSIONS: This study provides an initial understanding of comparative BVL for patients with RMS, encompassing an outcome not previously assessed in NMAs. Most DMTs were similar in their reductions in BVL when compared with teriflunomide, with some evidence favoring teriflunomide at 12 and 24 months.
